E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. Evaluate the safety and tolerability of VX-264 in subjects with T1D (Part A and Part B). 2. Evaluate VX-264 function in subjects with T1D (Part B and Part C). |
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E.2.2 | Secondary objectives of the trial |
1. Evaluate the effect of VX-264 on exogenous insulin dose (Part C). 2. Evaluate the effect of VX-264 on insulin independence (Part C). 3. Evaluate the effect of VX-264 on metabolic control (Part C). 4. Evaluate the safety and tolerability of VX-264 (Part C). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects (male and female) between the ages of 18 and 65 years (inclusive) on the date of first informed consent. 2. HbA1c ≥6.0% and ≤9.5%. 3. Clinical history and laboratory evidence of T1D based on the American Diabetes Association/European Association for the Study of Diabetes algorithm 13 for investigation of suspected T1D including: o insulin dependence for ≥5 years at time of Screening, and o peak stimulated C-peptide level during MMTT <50 pmol/L (<0.15 ng/mL) 4. Consistent use of CGM for at least 4 weeks before Screening and willingness to use only the study-provided CGM for the duration of the study. 5. Body habitus supportive of implantation of 6 VX-264 units. Please refer to Section 8.1 of the Protocol for additional inclusion criteria. |
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E.4 | Principal exclusion criteria |
1. Prior islet cell transplant, organ transplant, or cell therapy. 2. Advanced complications associated with diabetes including untreated proliferative retinopathy, diabetic nephropathy, skin ulcers, or amputations attributable to diabetes. 3. Insulin requirement: a) Parts A and B >40 U/day, or <10 U/day b) Part C: >55 U/day, or <10 U/day c) >0.8 U/kg/day. 4. Subjects with ≥2 or more episodes of severe hypoglycemia in the 12 months prior to signing of informed consent at Screening. 5. Previous abdominal or abdominal wall surgery, or history of peritonitis, that can impact VX-264 placement or put the patient at higher risk of surgical complications Please refer to Section 8.2 of the Protocol for additional exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A: Safety and tolerability assessments. Part B: - Safety and tolerability assessments, - Change from baseline in peak C-peptide during MMTT at Day 90. Part C: Change from baseline in peak C-peptide during MMTT at Day 90. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Please refer to the protocol |
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E.5.2 | Secondary end point(s) |
Part C: • Change from baseline in peak C-peptide during MMTT over time • Change from baseline in C-peptide AUC during MMTT over time • Proportion of subjects with peak C-peptide ≥100, ≥200, ≥400, and ≥1000 pmol/L (≥0.30, ≥0.60, ≥1.21, and ≥3.02 ng/mL) during MMTT over time • Change from baseline in average total daily insulin dose over time • Proportion of subjects with a reduction of at least 50% insulin dose from baseline and HbA1c <7.0% at Day 365 • Proportion of subjects who are insulin independent at one point in time between Day 180 and Day 365 • Change from baseline on metabolic control: HbA1c values; continuous glucose monitoring (CGM)-derived time-in-range (TIR) over time; glucose variability (CGM, CV%); and glucose management indicator (GMI) • Safety and tolerability assessments |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to the protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Netherlands |
Switzerland |
Germany |
Italy |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |